Nanocomposite sponges for enhancing intestinal residence time following oral administration

In this work, nanocomposites that combine mucopenetrating and mucoadhesive properties in a single system are proposed as innovative strategy to increase drug residence time in the intestine following oral administration. To this aim, novel mucoadhesive chitosan (CH) sponges loaded with mucopenetrating nanoemulsions (NE) were developed via freeze-casting technique.

Highlights
• Nanocomposites embedding nanoemulsions (NE) in chitosan (CH) sponges are produced by freeze-drying.

• The modulation of the nanocomposite structural features affects the stability of the sponge and the NE release profile in simulated intestinal environment.

• PEGylated NE shows effective mucopenetrating properties.

• The mucoadhesive ability of CH sponges concentrates NE at the intestinal site and increases the intestinal residence time following oral administration.

The NE mucopenetration ability was determined studying the surface affinity and thermodynamic binding of the nanosystem with mucins. The ability of nanoparticles to penetrate across a preformed mucins layer was validated by 3D-time laps Confocal Laser Scanning Microscopy imaging. Microscopy observation (Scanning Electron Microscopy and Optical Microscopy) showed that NE participated in the structure of the sponge affecting its stability and the in vitro release kinetics of NE. When incubated with HCT 116 and Caco-2 cell lines, the NE proved to be cytocompatible over a wide concentration range.

Finally, the in vivo biodistribution of the nanocomposite was evaluated after oral gavage in healthy mice. The intestinal retention of NE was highly enhanced when loaded in the sponge compared to the NE suspension. Overall, our results demonstrated that the developed nanocomposite sponge is a promising system for sustained drug intestinal delivery. Continue on Nanocomposite sponges for enhancing intestinal residence time following oral administration

Article information: Annalisa Rosso, Valentina Andretto, Yves Chevalier, David Kryza, Jacqueline Sidi-Boumedine, Ana Grenha, Filipa Guerreiro, Adem Gharsallaoui, Veronica La Padula, Alexandra Montembault, Laurent David, Stéphanie Briançon, Giovanna Lollo. Journal of Controlled Release, 2021. https://doi.org/10.1016/j.jconrel.2021.04.004.